Patients with large vessel occlusion (LVO) stroke achieved successful angiographic reperfusion after thrombectomy.

Results from the CHOICE-2 trial showed that adjunctive intra-arterial (IA) alteplase increased the likelihood of an excellent functional outcome by 15% without increasing bleeding risk and was associated with a 22% absolute reduction in abnormal microperfusion at follow-up.

“In patients with a successful angiographic result after thrombectomy, we can be misled into thinking complete perfusion has been achieved, but this might not be the case as thrombi often persist at the microcirculation level,” lead investigator, Ángel Chamorro, MD, professor of neurology at the University of Barcelona and head of the Comprehensive Stroke Center Hospital Clinic, Barcelona, Spain, told Medscape Medical News. 

“We showed that giving an intra-arterial thrombolytic after the large clot has been removed, significantly improved the microvascular circulation, and led to these very positive results,” he added. 

The findings were presented on February 4 at International Stroke Conference (ISC) 2026.

A Gamechanger?

Chamorro noted that a previous Chinese trial (PEARL) evaluated a similar approach and also showed a positive result. “There is now accumulating evidence in Asian and Caucasian populations that this is a highly effective therapy and that should change the whole landscape,” he said.

“This could be a game changer. CHOICE-2 supports the administration of IA alteplase after successful EVT [endovascular therapy] in selected patients,” he added.

Chamorro noted that despite successful angiographic reperfusion, fewer than one third of patients undergoing thrombectomy for LVO stroke achieve an excellent functional outcome (modified Rankin Scale [mRS] score of 0-1), and this angiographic-clinical mismatch is largely explained by persistent microvascular hypoperfusion.

“In other words, opening the artery does not always completely restore tissue perfusion,” he noted.

The initial CHOICE-1 trial tested the concept of treating beyond angiographic success and showed that adjunctive IA alteplase produced an 18-percentage-point absolute increase in the proportion of patients achieving a 90-day mRS score of 0-1.

However, this trial was stopped early for logistical reasons and so the CHOICE-2 trial was designed to validate these findings in a larger population.

Number Needed to Treat of Seven

The investigator-initiated, open-label, randomized trial with blinded assessment of clinical and imaging outcomes, was conducted at 14 centers in Spain.

It included 440 patients with LVO stroke who achieved successful reperfusion (TICI 2b or 3) with thrombectomy within 24 hours of symptom onset. Patients with very large strokes (National Institutes of Health Stroke Scale > 25) were excluded to minimize malignant edema and hemorrhagic risk.

After confirmation of successful reperfusion, patients were randomized to receive IA alteplase administered immediately after the final angiographic run at a low dose (0.225 mg/kg, maximum 20 mg) or no additional treatment.

Results showed that at 90 days, 57.5% of patients who received the IA alteplase achieved an mRS score 0-1 compared with 42.9% in the control group.

“This gives a highly significant 15-percentage-point adjusted risk difference, with a number needed to treat of just seven, to achieve one additional excellent outcome,” Chamorro said.

“This is almost exactly the same benefit as that seen with IV [intravenous] thrombolysis given in the first 3 hours after stroke onset compared to placebo.”

Other results showed that patients receiving IA alteplase had significantly less persistent hypoperfusion on CT perfusion imaging at 36 hours (29% vs 51%; P < .001), and functional independence and quality of life were also improved.

The treatment effect was consistent across prespecified subgroups, including those who had already received thrombolysis before thrombectomy.

There was no increase in symptomatic intracranial hemorrhage (1.4% in the IA alteplase group vs 0.5% in the control group; P = .33). “These are extremely low bleeding rates and the difference is negligible,” Chamorro noted.

Looking Beyond Angiographic Success

Mortality was numerically higher in the alteplase group (12% vs 6%), but Chamorro attributed this to “an unexpectedly low mortality in the control arm,” noting that CIs overlapped. But he added that the mortality difference requires further study.

He added that patients with complete normalization on angiography (TICI-3 flow) after thrombectomy who made up more than 50% of the study population, still showed benefit of IA alteplase.

The concept is that micro-clots form in situ in capillaries, said Chamorro. Once a large vessel is occluded, the lack of blood flow causes the formation of distal thrombin. So even if the main clot is successfully removed, these distal clots can remain, resulting in sub-optimal outcomes, he added.

This may be why only about one third of patients achieve excellent outcomes even when angiography looks normal following mechanical thrombectomy, he noted.

Patients at elevated bleeding risk were excluded from the trial and Chamorro estimated that those ultimately enrolled represented about 25% of all patients undergoing thrombectomy.

“We have to be conservative in initial trials to establish proof of concept, but then we can start opening the window further,” he said.

‘Great News’ for Stroke Care

Commenting on the findings for Medscape Medical News, Andrei Alexandrov, MD, chair of neurology, University of Arizona College of Medicine, and neurologist at Banner — University Medical Center in Phoenix, said the results were “great news.”

“A number needed to treat of seven shows a very large effect.”

Alexandrov explained that even after a successful mechanical thrombectomy with a good result, the patient often doesn’t recover completely.

“This trial shows that adding intra-arterial alteplase seems to improve delivery of blood flow to tissue on microscopic level, and that bears additional absolute benefit in terms of patient recovery to functional independence. This will be a significant improvement in stroke care because patients who get to thrombectomy are the most severely affected, so seeing that additional benefit really is wonderful.”

Alexandrov believes many interventionists will start using this approach in selected patients right away.

“I’m going to suggest we include it our protocols going forward. Obviously, there will be patients who will be unsuitable for this approach — anyone with a risk of hemorrhagic transformation, but we will follow the inclusion and exclusion criteria used in the trial,” he added.

The CHOICE-2 trail was funded by the Fundació de Recerca Clínic Barcelona – Institut d’Investigacions Biomèdiques August Pi i Sunyer. Chamorro reported receiving no relevant financial relationships.